"ALS is a horrific tragedy for those who suffer from it, and by no means do I or anyone associated with this film have anything but compassion for the individuals afflicted," MacFarlane said in a statement. "However, the joke in the film is made at the expense of our villain, Rex, and not at the expense of those suffering from the disease."

The joke, "From one man to another, I hope you get Lou Gehrig's disease," shocked movie-going patients and advocates, who say it crossed a line.

"I didn't expect to go to a movie and sit with an audience laughing at the expense of people with ALS," said Randy Pipkin, who was diagnosed in 2005. "I think the message this film sends out is a huge slap in the face to people dying from this horrific disease."

Lou Gehrig's disease, also known as ALS, progressively robs people of their ability to move, speak, eat and breathe. There is currently no cure.

The punch line prompted an online petition urging MacFarlane to apologize and donate $200,000 of the movie's proceedings to ALS research.

"The thing that Mr. MacFarlane and others fail to realize is that ALS sufferers are some of the kindest, compassionate, thoughtful, and loving individuals one will ever meet," Bridget Reeves Jeter, whose mother has ALS, wrote in the petition posted at Change.org. "Wishing ALS on another individual is really nothing but a foundationless insult, rather than an edgy, humorous scatological quip, as was intended."

But MacFarlane, 38, who is famous for his boundary-pushing humor, argues the "mere mention of any disease should not be cause for ire."

"I lost my mother to cancer, yet there is a joke in the film which contains the word cancer," he said. "I urge analysis of context, lest the 'outrage industry' get the better of us."

"We just want to stop this alarming trend before it becomes too widespread," Traci Bisson of the ALS Therapy Alliance, a Boston-based advocacy group, said in a statement. "We want to make it clear that ALS, or Lou Gehrig's disease, is not a laughing matter for people and families suffering from this life-threatening illness."

Actor Mark Wahlberg, who delivers the line, says he "had no idea" it would offend people with ALS.

"Obviously, you know, it wasn't our intention to really offend anybody," Wahlberg told "The Tommy Show" on 94.7 Fresh FM. "Seth wrote the material, so you've got to take it up with him."

"This line from Ted is something that never should have been said much less survived the editing process for a major movie release especially as a punch line for a comedy," Lester wrote in an open letter to MacFarlane and Wahlberg posted on Facebook. "From one man to another, I hope you or anyone you know or love NEVER GETS Lou Gehrig's disease."